A novel concept for low-cost non-electronic detection of overloading in the foot during activities of daily living

Identifying areas in the sole of the foot which are routinely overloaded during daily living is extremely important for the management of the diabetic foot. This work showcases the feasibility of reliably detecting overloading using a low-cost non-electronic technique. This technique uses thin-wall structures that change their properties differently when they are repeatedly loaded above or below a tuneable threshold. Flexible hexagonal thin-wall structures were produced using three-dimensional printing, and their mechanical behaviour was assessed before and after repetitive loading at different magnitudes. These structures had an elastic mechanical behaviour until a critical pressure (Pcrit = 252 kPa ± 17 kPa) beyond which they buckled. Assessing changes in stiffness after simulated use enabled the accurate detection of whether a sample was loaded above or below Pcrit (sensitivity = 100%, specificity = 100%), with the overloaded samples becoming significantly softer. No specific Pcrit value was targeted in this study. However, finite-element modelling showed that Pcrit can be easily raised or lowered, through simple geometrical modifications, to become aligned with established thresholds for overloading (e.g. 200 kPa) or to assess overloading thresholds on a patient-specific basis. Although further research is needed, the results of this study indicate that clinically relevant overloading could indeed be reliably detected without the use of complex electronic in-shoe sensors.


Introduction 1.
"Due to the key role repetitive overloading plays in the development of DFU, the reduction of plantar pressure is an important therapeutic objective in the clinical management of diabetic foot." Please, cite references at the end of this sentence to support your statement. I would suggest the more recent systematic review Netten, Jaap J.; Sacco, Isabel C.N. ; Lavery, Lawrence A.; Monteiro'soares, Matilde ; Rasmussen, Anne ; Raspovic, Anita ; Bus, Sicco A. Treatment of modifiable risk factors for foot ulceration in persons with diabetes: a systematic review. Diabetes-Metabolism Research And Reviews, v. 37, p. e3271, 2020. 2. "To promote evidence-based design of offloading interventions for the diabetic foot, thresholds of potentially injurious plantar pressure have been proposed in the literature (7-9)." Please, consider adding an important and recent reference from the guidelines that explicitly suggest a threshold, although still subject to criticism: Bus, Sicco A.; Lavery, Lawrence A. ; Monteiro'soares, Matilde ; Rasmussen, Anne; Raspovic, Anita; Sacco, Isabel C.N. ; Netten, Jaap J. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes-Metabolism Research And Reviews, v. 36, p. e3269, 2020. 3.
"Despite the mounting evidence in support of the use of plantar pressure measurements to inform footwear/orthoses prescription, such measurements are still not part of standard clinical practice." Consider adding a statement like "…, despite it is also recommended in the updated International Guidelines… Sensor development session 1.
Page 7, Line 10 -Please be consistent with the use of Pcrit (used in the text, abstract) or Pcr.

2.
Consider adding a paragraph discussing about the time needed to accumulate microdamage that would change the mechanical properties of the material, because if this is too much, maybe a DFU could occur before the material changes it mechanical linear properties, and the main aim of the insole to detect high pressures before an injury occur, would be compromised.

3.
The authors should consider explaining in this session (or in the methods) the routine imposed by the use of this new sensor to detect high pressures, that includes the patient to go to a specialized lab (not any lab) to evaluate the physical properties of the sensor after one day of receiving/using the sensor.

1.
The first paragraph is repeated in the previous session (1st paragraph of page 7). Maybe keeping only in the previous session would be enough or, even better, try to group the session 2 with session 3 (methods) and explain the sensor development in one only session.
Discussion and conclusion 1.
Overall, the discussion is straightforward and focused. My only suggestion is to discuss the values obtained in the tests with the suggested threshold in the literature, particularly in the International Guidelines. The value for buckling was surprisingly (and fortunately) very close to the suggested threshold for ulcer risk in the international guidelines. Even if this threshold is still questionable, it would be important to mention that in your paper: discussion and conclusion, as it makes your technique more plausible and considered adoptable worldwide.

2.
As one potential limitations of the technique, it would be interesting to add the need for the patient go to a very specialized lab that could measure the properties of the insole after the first day usage.

Decision letter (RSOS-202035.R0)
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General Comments
The goal of this manuscript was to showcase the feasibility of reliably detecting overloading using a low-cost non-electronic technique that uses thinwall structures that change their properties when they are routinely loaded above or below a tuneable threshold. The manuscript is solidly grounded and the proposal measurement technique is relevant. This is a bold and audacious proposal that will break paradigms on how to assess the risk of ulcers in people with diabetes and, perhaps, even change the modus operandi of regular evaluations needed for these people to avoid further complications such as amputations resulting from worsening of the disease. Although the introduction discussion need some additional work, the paper is straightforward and could be improved. There are some suggestions/comments that I addressed throughout the manuscript. Please, consider reviewing them. Abstract 1. In the abstract, it is important to describe clearly the threshold (Pcrit) adopted (or how they can be interchanged) and the rationale for it. 2. Please, add the value for buckling which was surprisingly (and fortunately) very close to the suggested threshold for ulcer risk in the international guidelines. Even if this threshold is still questionable, it would be important to mention that in your paper: abstract and conclusion, as it makes your technique more plausible and considered adoptable worldwide. Introduction 1. "Due to the key role repetitive overloading plays in the development of DFU, the reduction of plantar pressure is an important therapeutic objective in the clinical management of diabetic foot." Please, cite references at the end of this sentence to support your statement. I would suggest the more recent systematic review Netten, Jaap J.; Sacco, Isabel C.N. ; Lavery, Lawrence A.; Monteiro'soares, Matilde ; Rasmussen, Anne ; Raspovic, Anita ; Bus, Sicco A. Treatment of modifiable risk factors for foot ulceration in persons with diabetes: a systematic review. Diabetes-Metabolism Research And Reviews, v. 37, p. e3271, 2020. 2. "To promote evidence-based design of offloading interventions for the diabetic foot, thresholds of potentially injurious plantar pressure have been proposed in the literature (7-9)." Please, consider adding an important and recent reference from the guidelines that explicitly suggest a threshold, although still subject to criticism: Bus, Sicco A.; Lavery, Lawrence A. ; Monteiro'soares, Matilde ; Rasmussen, Anne; Raspovic, Anita; Sacco, Isabel C.N. ; Netten, Jaap J. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes-Metabolism Research And Reviews, v. 36, p. e3269, 2020. 3. "Despite the mounting evidence in support of the use of plantar pressure measurements to inform footwear/orthoses prescription, such measurements are still not part of standard clinical practice." Consider adding a statement like "…, despite it is also recommended in the updated International Guidelines… Sensor development session 1. Page 7, Line 10 -Please be consistent with the use of Pcrit (used in the text, abstract) or Pcr. 2. Consider adding a paragraph discussing about the time needed to accumulate microdamage that would change the mechanical properties of the material, because if this is too much, maybe a DFU could occur before the material changes it mechanical linear properties, and the main aim of the insole to detect high pressures before an injury occur, would be compromised. 3. The authors should consider explaining in this session (or in the methods) the routine imposed by the use of this new sensor to detect high pressures, that includes the patient to go to a specialized lab (not any lab) to evaluate the physical properties of the sensor after one day of receiving/using the sensor. Methods 1. The first paragraph is repeated in the previous session (1st paragraph of page 7). Maybe keeping only in the previous session would be enough or, even better, try to group the session 2 with session 3 (methods) and explain the sensor development in one only session.
Discussion and conclusion 1. Overall, the discussion is straightforward and focused. My only suggestion is to discuss the values obtained in the tests with the suggested threshold in the literature, particularly in the International Guidelines. The value for buckling was surprisingly (and fortunately) very close to the suggested threshold for ulcer risk in the international guidelines. Even if this threshold is still questionable, it would be important to mention that in your paper: discussion and conclusion, as it makes your technique more plausible and considered adoptable worldwide. 2. As one potential limitations of the technique, it would be interesting to add the need for the patient go to a very specialized lab that could measure the properties of the insole after the first day usage.

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Author's Response to Decision Letter for (RSOS-202035.R0) See Appendix A.

Comments to the Author(s)
The paper sounds much better, the additions implemented contributed for improving the clarity and clinical usefulness of the results.

Decision letter (RSOS-202035.R1)
We hope you are keeping well at this difficult and unusual time. We continue to value your support of the journal in these challenging circumstances. If Royal Society Open Science can assist you at all, please don't hesitate to let us know at the email address below.

Dear Dr Chatzistergos,
It is a pleasure to accept your manuscript entitled "A novel concept for low-cost non-electronic detection of overloading in the foot during activities of daily living." in its current form for publication in Royal Society Open Science. The comments of the reviewer(s) who reviewed your manuscript are included at the foot of this letter.
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General Comments
The goal of this manuscript was to showcase the feasibility of reliably detecting overloading using a low-cost non-electronic technique that uses thinwall structures that change their properties when they are routinely loaded above or below a tuneable threshold. The manuscript is solidly grounded and the proposal measurement technique is relevant. This is a bold and audacious proposal that will break paradigms on how to assess the risk of ulcers in people with diabetes and, perhaps, even change the modus operandi of regular evaluations needed for these people to avoid further complications such as amputations resulting from worsening of the disease.
Although the introduction discussion need some additional work, the paper is straightforward and could be improved. There are some suggestions/comments that I addressed throughout the manuscript. Please, consider reviewing them.
The authors would like to thank the reviewer for their positive feedback, helpful comments and valuable suggestions. The manuscript is now revised to address the reviewer's comments. Each comment is followed by the response of the authors (in underlined italics) and a short description of the action undertaken. In case a part of the text is rewritten, or new material is added the new version is also included (centrally justified italics). For your convenience all revisions are highlighted in the revised manuscript. Abstract 1. In the abstract, it is important to describe clearly the threshold (Pcrit) adopted (or how they can be interchanged) and the rationale for it. 2. Please, add the value for buckling which was surprisingly (and fortunately) very close to the suggested threshold for ulcer risk in the international guidelines. Even if this threshold is still questionable, it would be important to mention that in your paper: abstract and conclusion, as it makes your technique more plausible and considered adoptable worldwide.
We agree with the reviewer's recommendations regarding the abstract. To address these two comments the value of the overloading threshold (Pcrit ) is added in the revised abstract. Moreover, the closing section of the abstract is also rewritten as follows to include a brief discussion into the relevance of Pcrit with existing pressure thresholds used in diabetic foot management, as well as an explanation on how Pcrit can be tuned and the rationale behind its tunning.